The complications of diabetes mellitus continue to be a major source of morbidity and early mortality but have not yet been comprehensively studied from an epidemiological viewpoint. The prevalence, incidence and interrelationships between the four major complications (i.e., retinopathy, nephropathy, neuropathy, and macrovascular disease) of insulin-dependent diabetes mellitus (IDDM) and their risk factors are being examined in a ten year prospective study of IDDM subjects diagnosed in childhood. Risk factors and complications status are determined on a biennial basis. The study population is a well-defined cohort of IDDM patients identified from the Children's Hospital of Pittsburgh IDDM Registry. This registry included 70% of patients diagnosed under the age of 17 years in Allegheny County and is representative of the county-wide childhood diabetic population. The prevalence rates of the four major complications have been determined at baseline exam (1986-88) in this cohort of 657 IDDM participants diagnosed between 1/1/50 and 5/31/80. At baseline they were aged 8-48 years and had a duration of diabetes spanning from 8 to 37 years. Cycle II examinations are currently in progress. In the proposed study period, a further two cycles of biennial exams will be completed using the same methodology for complication endpoints: retinopathy (stereo fundus photography), nephropathy (AER from three timed urine samples), neuropathy (DCCT protocol), peripheral vascular disease (ankle/arm blood pressure ratios after exercise), cardiovascular disease (validated MI or angina). In addition to current risk factors [e.g., lipids, apolipoproteins, platelet aggregation, GHb, blood pressure, behavioral risk factors (including smoking, alcohol, physical activity, and diet)), new factors will be measured in the proposed grant period, including Na-Li countertransport and Lp(a). A substudy will also examine carotid artery disease (ultrasonography) and arterial calcification (foot x-rays). In this way, we will identify the risk factors responsible for complications prospectively and be able to examine the interrelationships of IDDM complications. This should lead to the development of appropriate preventive strategies.